Deracemization of Acyclic α-Hydroxy Ketone Derivatives by Dynamic Resolution Using an Optically Active Host Compound

Abstract

The dynamic resolution of racemic acyclic α-hydroxy ketone derivatives is accomplished using an optically active host compound, TADDOL, under basic conditions to give the corresponding optically active ketones.

acyclic ketones - deracemization - enantiomeric resolution - host-guest systems - optically active compounds

References and Notes

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<A NAME="RU14906ST-12">12</A>

The substrate (±)-1 was easily prepared from (±)-lactic acid in four steps. The details of this synthesis have been reported in ref. 13.

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<A NAME="RU14906ST-14">14</A>

The absolute configuration of 1 was confirmed by comparing the obtained optical rotation value with the reported value: Lit. [21] [α]_D ²⁴ -45.9 (c 1.16, CHCl₃), S-form.

<A NAME="RU14906ST-15">15</A>

The ee of 1 was determined by HPLC analysis with CHIRALCEL OJ (Daicel Chemical Industries, Ltd.); eluent, hexane-2-PrOH = 180:1; flow rate, 0.5 mL min^-1; t _R = 40 (R) and 50 (S) min.

<A NAME="RU14906ST-16">16</A>

The deracemization did not occur for the reactions using the other TADDOL derivatives bearing a cyclopentane ring and a dimethyl group [(-)-2,2-tetramethylene- and 2,2-dimethyl-α,α,α′,α′-tetraphenyl-1,3-dioxolan-4,5-dimethanol, respectively], (+)-1,1′-bi-2-naphthol, and (-)-hydrobenzoin as chiral host compounds under the same conditions.

<A NAME="RU14906ST-17">17</A>

Although the ee of (S)-1 increased according to the extension of the reaction time (42% ee for one day), the reaction for over three days gave almost the same result as that of the three-day reaction. We then decided that the racemizations in all cases were carried out for three days.

<A NAME="RU14906ST-18">18</A>

The reaction using EtOH, i-PrOH, t-BuOH, and cyclohexane as an alternative mix solvent with H₂O gave only the racemate 1.

<A NAME="RU14906ST-19">19</A>

A white solid was obtained by filtration when a sat. NH₄Cl aq and EtOAc were not added to the reaction mixture. ESI-TOFMS analysis of the collected solid showed the peak of [1 + 2 + Na]⁺ ion (m/z = 721.3 for C₄₆H₅₀O₆Na) in the same manner as the case of the optical resolution. [13] The peak would mean the construction of the 1:1 inclusion complex (1 and 2) in the reaction mixture.

<A NAME="RU14906ST-20">20</A>

The ee of the products can be improved by a sequential optical resolution using (-)-2 without a base. [13]

<A NAME="RU14906ST-21">21</A> Matsumoto K. Suzuki N. Ohta H. Tetrahedron Lett.  1990,  31:  7159